Studies with first episode populations offer the unique opportunity to examine the role of medications without the confounding effects of prior medication use. In addition, successful treatment of the initial psychotic episode is crucial for minimizing the cascading effects of social and vocational deterioration. The current application is a competing renewal of the Preventing Morbidity in First Episode Schizophrenia study (MH60004) that compared treatment with olanzapine and risperidone, the two most widely used second generation antipsychotics. In contrast to our expectations, our data show medication differences favoring risperidone in positive symptom reduction, but not negative symptom reduction or cognitive function. However, both olanzapine and risperidone caused very rapid, substantial initial weight gain (18% and 11% of baseline weight for subjects assigned to olanzapine and risperidone respectively) over the first 4 months of treatment. By three years subjects gained 30% of their baseline weight. This degree of weight gain clearly has important implications for quality of life and has long-term health consequences. Newer second generation antipsychotics with lower risks of weight gain and other metabolic side effects are now available, but little is known about their efficacy for first episode subjects, or their efficacy in comparison to risperidone or olanzapine. A crucial question is how much, if any, tradeoff in effectiveness would result if a low weight-gain second generation antipsychotic were used in place of a more widely used second generation antipsychotic. We propose a 12- week random-assignment, double-blind trial comparing risperidone with aripiprazole, a second generation antipsychotic with a lower risk of metabolic side effects, as first treatment for subjects with schizophrenia spectrum disorders. In addition to the multi-dimensional assessment of treatment outcomes in our current study, the proposed study will feature a more comprehensive assessment of side effects with a focus upon metabolic and other side effects with important health consequences. To enhance generalizability of the findings, we will recruit subjects from settings serving diverse ethnic groups and use broad inclusion criteria. A sample of 242 subjects will be recruited, with the expectation that 202 will complete the 12-week trial. The findings will provided guidance to clinicians in the selection of the best medication for patients experiencing a first episode of illness, who have no prior treatment history to guide this choice.